tbuckley/cabot-search huggingface dataset:
Design and fabrication of high-performance injectable self-setting trimagnesium phosphate
Authors: Jiawei Liu, Wen Hou, Wenying Wei, Jian Peng, Xiaopei Wu, Chenxi Lian, Yanan Zhao, Rong Tu, Takashi Goto, Honglian Dai
Journal: Bioactive Materials (2023)

Magnesium phosphate bone cement has become a widely used orthopedic implant due to the advantages of fast-setting and high early strength. However, developing magnesium phosphate cement possessing applicable injectability, high strength, and biocompatibility simultaneously remains a significant challenge. Herein, we propose a strategy to develop high-performance bone cement and establish a trimagnesium phosphate cement (TMPC) system. The TMPC exhibits high early strength, low curing temperature, neutral pH, and excellent injectability, overcoming the critical limitations of recently studied magnesium phosphate cement. By monitoring the hydration pH value and electroconductivity, we demonstrate that the magnesium-to-phosphate ratio could manipulate the components of hydration products and their transformation by adjusting the pH of the system, which will influence the hydration speed. Further, the ratio could regulate the hydration network and the properties of TMPC. Moreover, in vitro studies show that TMPC has outstanding biocompatibility and bone-filling capacity. The facile preparation properties and these advantages of TMPC render it a potential clinical alternative to polymethylmethacrylate and calcium phosphate bone cement. This study will contribute to the rational design of high-performance bone cement.
Natural history of NASH cirrhosis in liver transplant waitlist registrants
Authors: Wen Hui Lim, Cheng Han Ng, Darren Tan, Michael Tseng, Jieling Xiao, Jie Ning Yong, Rebecca Wenling Zeng, Elina Cho, Phoebe Tay, Chong Zhe Ang, Jia Hong Koh, Margaret Teng, Nicholas Syn, Alfred Kow, Daniel Q. Huang, Eunice XX. Tan, Mary E. Rinella, Arun Sanyal, Mark Muthiah, Mohammad Shadab Siddiqui
Journal: Journal of Hepatology (2023)
High levels of intracellular endotrophin in adipocytes mediate COPII vesicle supplies to autophagosome to impair autophagic flux and contribute to systemic insulin resistance in obesity
Authors: Jiyoung Oh, Chanho Park, Sahee Kim, Min Kim, Chu-Sook Kim, Woobeen Jo, Sungho Park, Gwan-Su Yi, Jiyoung Park
Journal: Metabolism (2023)
A Diagnosis of Irritable Bowel Syndrome Using Rome IV Criteria and Limited Investigations is Durable in Secondary Care
Authors: Mais Khasawneh, Orla F. Craig, David J. Gracie, Christopher J. Black, Alexander C. Ford
Journal: Clinical Gastroenterology and Hepatology (2023)

Irritable bowel syndrome (IBS) is a positive diagnosis, made using symptom-based criteria and limited, judicious, investigation. However, this may lead to uncertainty on the part of clinicians regarding potential for a missed diagnosis of organic gastrointestinal disease. Few studies have examined durability of a diagnosis of IBS, and none have used the current gold standard to diagnose IBS, the Rome IV criteria.
All-in-one glycol chitosan nanoparticles for co-delivery of doxorubicin and anti-PD-L1 peptide in cancer immunotherapy
Authors: Sukyung Song, Man Kyu Shim, Suah Yang, Jaewan Lee, Wan Su Yun, Hanhee Cho, Yujeong Moon, Jin Young Min, Eun Hee Han, Hong Yeol Yoon, Kwangmeyung Kim
Journal: Bioactive Materials (2023)

Synergistic immunotherapy of immune checkpoint blockade (ICB) and immunogenic cell death (ICD) has shown remarkable therapeutic efficacy in various cancers. However, patients show low response rates and undesirable outcomes to these combination therapies owing to the recycling mechanism of programmed death-ligand 1 (PD-L1) and the systemic toxicity of ICD-inducing chemotherapeutic drugs. Herein, we propose all-in-one glycol chitosan nanoparticles (CNPs) that can deliver anti-PD-L1 peptide (PP) and doxorubicin (DOX) to targeted tumor tissues for a safe and more effective synergistic immunotherapy. The PP-CNPs, which are prepared by conjugating ᴅ-form PP (NYSKPTDRQYHF) to CNPs, form stable nanoparticles that promote multivalent binding with PD-L1 proteins on the targeted tumor cell surface, resulting in effective lysosomal PD-L1 degradation in contrast with anti-PD-L1 antibody, which induces recycling of endocytosed PD-L1. Consequently, PP-CNPs prevent subcellular PD-L1 recycling and eventually destruct immune escape mechanism in CT26 colon tumor-bearing mice. Moreover, the ICD inducer, DOX is loaded into PP-CNPs (DOX-PP-CNPs) for synergistic ICD and ICB therapy, inducing a large number of damage-associated molecular patterns (DAMPs) in targeted tumor tissues with minimal toxicity in normal tissues. When the DOX-PP-CNPs are intravenously injected into CT26 colon tumor-bearing mice, PP and DOX are efficiently delivered to the tumor tissues via nanoparticle-derived passive and active targeting, which eventually induce both lysosomal PD-L1 degradation and substantial ICD, resulting in a high rate of complete tumor regression (CR: 60%) by a strong antitumor immune response. Collectively, this study demonstrates the superior efficacy of synergistic immunotherapy using all-in-one nanoparticles to deliver PP and DOX to targeted tumor tissues.
Could chronic HBV infection explain Beethoven's hearing loss? Implications for patients currently living with hepatitis B
Authors: Piotr Rzymski, Dorota Zarębska-Michaluk, Robert Flisiak
Journal: Journal of Infection (2023)

The cause of Ludwig van Beethoven's health deterioration, i.e., hearing loss and cirrhosis, have been subject to various studies. The genomic analysis of his hair indicates infection with the hepatitis B virus (HBV) at least 6 months prior to death. However, considering his first documented case of jaundice in the summer of 1821, second jaundice months prior to his death, and increased risk of hearing loss in HBV-infected patients, we offer an alternative hypothesis of chronic HBV infection as a cause of deafness and cirrhosis. According to it, HBV was acquired early, progressed from immune-tolerant to an immune-reactive phase, and triggered Beethoven's hearing issues when aged 28. Later, HBV infection entered the non-replication phase with at least two episodes of reactivation in the fifth decade of life accompanied by jaundice. More studies examining hearing loss in patients with chronic HBV infection are encouraged to better understand their potential otologic needs.
Toward antivirals against hepatitis E: In the steps of hepatitis C
Authors: Jérôme Gouttenoire, Johan Neyts
Journal: Hepatology (2023)

1Division of Gastroenterology and Hepatology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland 2KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium Correspondence Jérôme Gouttenoire. Email: [email protected]; [email protected]
Immune effector cell–associated hematotoxicity: EHA/EBMT consensus grading and best practice recommendations
Authors: Kai Rejeski, Marion Subklewe, Mahmoud Aljurf, Emmanuel Bachy, Adriana Balduzzi, Pere Barba, Benedetto Bruno, Reuben Benjamin, Matteo G. Carrabba, Christian Chabannon, Fabio Ciceri, Paolo Corradini, Julio Delgado, Roberta Di Blasi, Raffaella Greco, Roch Houot, Gloria Iacoboni, Ulrich Jäger, Marie José Kersten, Stephan Mielke, Arnon Nagler, Francesco Onida, Zinaida Peric, Claire Roddie, Annalisa Ruggeri, Fermín Sánchez-Guijo, Isabel Sánchez-Ortega, Dominik Schneidawind, Maria-Luisa Schubert, John A. Snowden, Catherine Thieblemont, Max Topp, Pier Luigi Zinzani, John G. Gribben, Chiara Bonini, Anna Sureda, Ibrahim Yakoub-Agha
Journal: Blood (2023)

Abstract Hematological toxicity is the most common adverse event after chimeric antigen receptor (CAR) T-cell therapy. Cytopenias can be profound and long-lasting and can predispose for severe infectious complications. In a recent worldwide survey, we demonstrated that there remains considerable heterogeneity in regard to current practice patterns. Here, we sought to build consensus on the grading and management of immune effector cell–associated hematotoxicity (ICAHT) after CAR T-cell therapy. For this purpose, a joint effort between the European Society for Blood and Marrow Transplantation (EBMT) and the European Hematology Association (EHA) involved an international panel of 36 CAR T-cell experts who met in a series of virtual conferences, culminating in a 2-day meeting in Lille, France. On the basis of these deliberations, best practice recommendations were developed. For the grading of ICAHT, a classification system based on depth and duration of neutropenia was developed for early (day 0-30) and late (after day +30) cytopenia. Detailed recommendations on risk factors, available preinfusion scoring systems (eg, CAR-HEMATOTOX score), and diagnostic workup are provided. A further section focuses on identifying hemophagocytosis in the context of severe hematotoxicity. Finally, we review current evidence and provide consensus recommendations for the management of ICAHT, including growth factor support, anti-infectious prophylaxis, transfusions, autologous hematopoietic stem cell boost, and allogeneic hematopoietic cell transplantation. In conclusion, we propose ICAHT as a novel toxicity category after immune effector cell therapy, provide a framework for its grading, review literature on risk factors, and outline expert recommendations for the diagnostic workup and short- and long-term management.
The multifaceted landscape behind imatinib resistance in gastrointestinal stromal tumors (GISTs): A lesson from ripretinib
Authors: Aldo Di Vito, Gloria Ravegnini, Francesca Gorini, Trond Aasen, César Serrano, Eva Benuzzi, Emma Coschina, Sarah Monesmith, Fabiana Morroni, Sabrina Angelini, Patrizia Hrelia
Journal: Pharmacology & Therapeutics (2023)

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal sarcomas and the gold-standard treatment is represented by tyrosine kinase inhibitors (TKIs). Unfortunately, first-line treatment with the TKI imatinib usually promotes partial response or stable disease rather than a complete response, and resistance appears in most patients. Adaptive mechanisms are immediately relevant at the beginning of imatinib therapy, and they may represent the reason behind the low complete response rates observed in GISTs. Concurrently, resistant subclones can silently continue to grow or emerge de novo, becoming the most representative populations. Therefore, a slow evolution of the primary tumor gradually occurs during imatinib treatment, enriching heterogeneous imatinib resistant clonal subpopulations. The identification of secondary KIT/PDGFRA mutations in resistant GISTs prompted the development of novel multi-targeted TKIs, leading to the approval of sunitinib, regorafenib, and ripretinib. Although ripretinib has broad anti-KIT and -PDGFRA activity, it failed to overcome sunitinib as second-line treatment, suggesting that imatinib resistance is more multifaceted than initially thought. The present review summarizes several biological aspects suggesting that heterogeneous adaptive and resistance mechanisms can also be driven by KIT or PDGFRA downstream mediators, alternative kinases, as well as non-coding RNAs, which are not targeted by any TKI, including ripretinib. This may explain the modest effect observed with ripretinib and all anti-GIST agents in patients.
Targeting cytokine-like protein FAM3D lowers blood pressure in hypertension
Authors: Yicong Shen, Zhigang Dong, Fangfang Fan, Kaiyin Li, Shirong Zhu, Rongbo Dai, Jiaqi Huang, Nan Xie, Li He, Ze Gong, Xueyuan Yang, Jiaai Tan, Limei Liu, Fang Yu, Yida Tang, Zhen You, Jianzhong Xi, Ying Wang, Wei Kong, Yan Zhang, Yi Fu
Journal: Cell Reports Medicine (2023)

Current antihypertensive options still incompletely control blood pressure, suggesting the existence of uncovered pathogenic mechanisms. Here, whether cytokine-like protein family with sequence similarity 3, member D (FAM3D) is involved in hypertension etiology is evaluated. A case-control study exhibits that FAM3D is elevated in patients with hypertension, with a positive association with odds of hypertension. FAM3D deficiency significantly ameliorates angiotensin II (AngII)-induced hypertension in mice. Mechanistically, FAM3D directly causes endothelial nitric oxide synthase (eNOS) uncoupling and impairs endothelium-dependent vasorelaxation, whereas 2,4-diamino-6-hydroxypyrimidine to induce eNOS uncoupling abolishes the protective effect of FAM3D deficiency against AngII-induced hypertension. Furthermore, antagonism of formyl peptide receptor 1 (FPR1) and FPR2 or the suppression of oxidative stress blunts FAM3D-induced eNOS uncoupling. Translationally, targeting endothelial FAM3D by adeno-associated virus or intraperitoneal injection of FAM3D-neutralizing antibodies markedly ameliorates AngII- or deoxycorticosterone acetate (DOCA)-salt-induced hypertension. Conclusively, FAM3D causes eNOS uncoupling through FPR1- and FPR2-mediated oxidative stress, thereby exacerbating the development of hypertension. FAM3D may be a potential therapeutic target for hypertension.
Beyond One-Size-Fits-All: Size-Oriented Criteria for the Step-Up Treatment of Walled-Off Pancreatic Necrosis
Authors: Tsuyoshi Hamada, Masahiro Tsujimae, Yousuke Nakai, Tomotaka Saito, Atsuhiro Masuda, Mamoru Takenaka, Hideyuki Shiomi, Hiroyuki Isayama, Takuji Iwashita, Ichiro Yasuda
Journal: Clinical Gastroenterology and Hepatology (2023)
Can surgery induce cancer recurrence or metastasis? -revisiting the relationship between anesthetic selection and outcomes in cancer surgery
Authors: Saravanan Sekaran, Vimalraj Selvaraj, Dhanraj Ganapathy, Sureh Kumar Rajamani Sekar
Journal: International Journal of Surgery (2023)

Sekaran, Saravanan; Selvaraj, Vimalraj; Ganapathy, Dhanraj; Rajamani Sekar, Sureh Kumar Author Information
Control of drug release kinetics from hot-melt extruded drug-loaded polycaprolactone matrices
Authors: Yun-Chu Chen, Sota Shishikura, Dana E. Moseson, Austin J. Ignatovich, Joshua Lomeo, Aiden Zhu, Sarena D. Horava, Coralie A. Richard, Kinam Park, Yoon Yeo
Journal: Journal of Controlled Release (2023)
Low-dose intrapulmonary drug delivery device for studies on next-generation therapeutics in mice
Authors: Ana Maria Gracioso Martins, Douglas B. Snider, Kristen D. Popowski, Karl G. Schuchard, Matias Tenorio, Sandip Akunuri, Junghyun Wee, Kara J. Peters, Anton Jansson, Rohan Shirwaiker, Ke Cheng, Donald O. Freytes, Glenn P. Cruse
Journal: Journal of Controlled Release (2023)
HLA-II immunopeptidome profiling and deep learning reveal features of antigenicity to inform antigen discovery
Authors: Martin Stražar, Jihye Park, Jennifer G. Abelin, Hannah B. Taylor, Thomas K. Pedersen, Damian R. Plichta, Eric M. Brown, Basak Eraslan, Yuan-Mao Hung, Kayla Ortiz, Karl R. Clauser, Steven A. Carr, Ramnik J. Xavier, Daniel B. Graham
Journal: Immunity (2023)
Mesenchymal Hamartoma of the Liver and DICER1 Syndrome
Authors: Maria Apellaniz-Ruiz, Maria Segni, Matthias Kettwig, Sylvia Glüer, Dylan Pelletier, Van-Hung Nguyen, Rabea Wagener, Cristina López, Karl Muchantef, Dorothée Bouron-Dal Soglio, Nelly Sabbaghian, Mona K. Wu, Stefano Zannella, Marc R. Fabian, Reiner Siebert, Jan Menke, John R. Priest, William D. Foulkes
Journal: New England Journal of Medicine (2019)
A trans-amplifying RNA simplified to essential elements is highly replicative and robustly immunogenic in mice
Authors: Mario Perkovic, Stefanie Gawletta, Tina Hempel, Silke Brill, Evelin Nett, Ugur Sahin, Tim Beissert
Journal: Molecular Therapy (2023)

(Molecular Therapy 31, 1636–1646; June 2023) In the originally published version of this article, a number of transreplicon sequences provided in Table S1 were misspelled. During the revision and publication process, one superfluous and potentially harmful “G” was added unintentionally downstream to the first transcribed nucleotide following the T7 polymerase promoter. Upon in vitro transcription, resulting transcripts would start with 5’-GGAU…-3’. This erroneous extension of the 5’end could affect replication. The correct 5’end should be 5’-GAU…-3’. This has been corrected online, and the authors apologize for this error. A trans-amplifying RNA simplified to essential elements is highly replicative and robustly immunogenic in micePerkovic et al.Molecular TherapyJanuary 23, 2023In BriefThis work presents the improvement of trans-amplifying RNA (taRNA), a bipartite vector system aiming to accelerate RNA vaccine adaptation by using an mRNA-encoded alphaviral replicase that amplifies minimal amounts of antigen-coding transreplicon RNA. The transreplicon design was streamlined to improve taRNA safety, and a directed evolution approach increased its potency. Full-Text PDF
Heparin induced thrombocytopenia
Authors: L.-A. Linkins
Journal: BMJ (2015)

This clinical review has been developed for <i>The BMJ</i> in collaboration with BMJ Best Practice, based on a regularly updated web/mobile topic that supports evidence based decision making at the point of care. To view the complete and current version, please refer to the heparin induced thrombocytopenia (http://bestpractice.bmj.com/best-practice/monograph/1202.html) topic on the BMJ Best Practice website.
Exosomes in brain diseases: Pathogenesis and therapeutic targets
Authors: Qingying Si, Linlin Wu, Deshui Pang, Pei Jiang
Journal: MedComm (2023)

Exosomes are extracellular vesicles with diameters of about 100 nm that are naturally secreted by cells into body fluids. They are derived from endosomes and are wrapped in lipid membranes. Exosomes are involved in intracellular metabolism and intercellular communication. They contain nucleic acids, proteins, lipids, and metabolites from the cell microenvironment and cytoplasm. The contents of exosomes can reflect their cells' origin and allow the observation of tissue changes and cell states under disease conditions. Naturally derived exosomes have specific biomolecules that act as the "fingerprint" of the parent cells, and the contents changed under pathological conditions can be used as biomarkers for disease diagnosis. Exosomes have low immunogenicity, are small in size, and can cross the blood-brain barrier. These characteristics make exosomes unique as engineering carriers. They can incorporate therapeutic drugs and achieve targeted drug delivery. Exosomes as carriers for targeted disease therapy are still in their infancy, but exosome engineering provides a new perspective for cell-free disease therapy. This review discussed exosomes and their relationship with the occurrence and treatment of some neuropsychiatric diseases. In addition, future applications of exosomes in the diagnosis and treatment of neuropsychiatric disorders were evaluated in this review.
Targeting KAT2A inhibits inflammatory macrophage activation and rheumatoid arthritis through epigenetic and metabolic reprogramming
Authors: Yunkai Zhang, Ying Gao, Yingying Ding, Yuyu Jiang, Huiying Chen, Zhenzhen Zhan, Xingguang Liu
Journal: MedComm (2023)

Epigenetic regulation of inflammatory macrophages governs inflammation initiation and resolution in the pathogenesis of rheumatoid arthritis (RA). Nevertheless, the mechanisms underlying macrophage-mediated arthritis injuries remain largely obscure. Here, we found that increased expression of lysine acetyltransferase 2A (KAT2A) in synovial tissues was closely correlated with inflammatory joint immunopathology in both RA patients and experimental arthritis mice. Administration of MB-3, the KAT2A-specific chemical inhibitor, significantly ameliorated the synovitis and bone destruction in collagen-induced arthritis model. Both pharmacological inhibition and siRNA silencing of KAT2A, not only suppressed innate stimuli-triggered proinflammatory gene (such as
Might It Be Appropriate to Anticipate the Use of Long-Acting Muscarinic Antagonists in Asthma?
Authors: Mario Cazzola, Paola Rogliani, Maria Gabriella Matera
Journal: Drugs (2023)

A growing number of clinical trials are documenting that adding a long-acting muscarinic antagonist (LAMA) to established asthma treatment with an inhaled corticosteroid (ICS) and a long-acting β2-agonist (LABA) is a treatment option that improves the health of patients with uncontrolled severe asthma even when therapy is optimized. These favorable results are the reason why the leading guidelines recommend triple therapy with ICS + LABA + LAMA in patients with asthma uncontrolled by medium- to high-dose ICS-LABA. However, we suggest adding LAMAs to ICS-LABAs at an earlier clinical stage. Such action could positively influence airflow limitation, exacerbations, and eosinophilic inflammation, conditions that are associated with acetylcholine (ACh) activity. It could also interrupt the vicious cycle related to a continuous release of ACh leading to the progressive expansion of neuronal plasticity resulting in small airway dysfunction. The utility of an earlier use of triple therapy in asthma should, in any case, be confirmed by statistically powered trials.
Updates on Recent Clinical Assessment of Commercial Chronic Wound Care Products
Authors: Archita Sharma, Dhavan Sharma, Feng Zhao
Journal: Advanced Healthcare Materials (2023)

Impaired wound healing after trauma, disorders, and surgeries impact millions of people globally every year. Dysregulation in orchestrated healing mechanisms and underlying medical complications make chronic wound management extremely challenging. Besides standard-of-care treatments including broad spectrum antibiotics and wound-debridement, novel adjuvant therapies are clinically tested and commercialized. These include topical agents, skin substitutes, growth factor delivery, and stem cell therapies. With a goal to overcome factors playing pivotal role in delayed wound healing, researchers are exploring novel approaches to elicit desirable healing outcomes in chronic wounds. Although recent innovations in wound care products, therapies, and devices are extensively reviewed in past, a comprehensive review summarizing their clinical outcomes is surprisingly lacking. Herein, this work reviews the commercially available wound care products and their performance in clinical trials to provide a statistically comprehensive understanding of their safety and efficacy. The performance and suitability of various commercial wound care platforms, including xenogeneic and allogenic products, wound care devices, and novel biomaterials, are discussed for chronic wounds. The current clinical evaluation will provide a comprehensive understanding of the benefits and drawbacks of the most-recent approaches and will enable researchers and healthcare providers to develop next-generation technologies for chronic wound management.
Peripheral biomarkers for predicting sputum eosinophilia in nonsteroidal anti‐inflammatory drug‐exacerbated respiratory disease
Authors: Gabriela Trąd, Marek Sanak, Adam Ćmiel, Natalia Celejewska‐Wójcik, Michał Czekaj, Lucyna Mastalerz
Journal: Allergy (2023)

The data that support the findings of this study are available from the corresponding author upon reasonable request. Data S1 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.